Kristine Krafts, M.D.Chronic Leukemia, Lymphoma, and Myeloma

Leukemias• Acute leukemias• Chronic leukemias

Lymphomas• Non-Hodgkin lymphoma• Hodgkin lymphoma

Plasma cell disorders• Multiple myeloma

Hematologic Malignancies

Leukemias• Acute leukemias• Chronic leukemias

Hematologic Malignancies

Chronic myeloid leukemia Chronic lymphocytic leukemia

• Malignant proliferation of myeloid cells (not blasts, but maturing cells) in blood, bone marrow

• Many disorders; CML most important

• Occur only in adults

• Long course

Chronic Myeloproliferative Disorders

Things You Must Know

• Neutrophilic leukocytosis

• Basophilia

• Philadelphia chromosome

• Three phases

Chronic Myeloid Leukemia

Things You Must Know

Chronic Myeloid Leukemia

Chronic Myeloid Leukemia

All cases of CML have the Philadelphia chromosome!

t(9;22)

9

22

BCR

ABL

9

22

BCR-ABL fusion gene

NASTYtyrosine kinase

Chronic phase• Stable counts (Hgb, WBC, platelets)• 3-4 years (without therapy)

Accelerated phase• Unstable counts• Fatal within months

Blast crisis• Lots of blasts (basically, acute leukemia!)• Fatal within weeks

Phases of CML

Treatment• Used to be bone marrow transplant• Now, imatinib (Gleevec)

Prognosis• Median survival used to be 5-6 years• Now: ??

Treatment and Prognosis of CML

• Malignant proliferation of lymphocytes in blood, bone marrow

• Many disorders; CLL most important

• Occur only in adults

• Long course; indolent but incurable

Chronic Lymphoproliferative Disorders

Things You Must Know

• Most common leukemia in adults

• Small, mature B lymphocytes

• Weird immunophenotype: CD5+

• Decreased normal immunoglobulins

Chronic Lymphocytic Leukemia

Things You Must Know

CLL: tons of mature-appearing lymphocytes in blood

CLL: tumor aggregates in marrow

Leukemias• Acute leukemias• Chronic leukemias

Lymphomas• Non-Hodgkin lymphoma• Hodgkin lymphoma

Hematologic Malignancies

• Malignant proliferation of lymphocytes that starts in lymph nodes

• Skips around• Many different types• Prognosis depends on specific type

Things you must know

Non-Hodgkin Lymphoma

• Painless, firm lymphadenopathy• Extranodal manifestations• “B” symptoms: weight loss,

night sweats, fever

Symptoms of NHL

• Most common cause overall: benign reaction to infection

• Most common malignant cause: metastatic carcinoma

Note: Most cases of lymphadenopathy are NOT due to lymphoma!

Composed of small, mature, slowly-growing cells.

Low-grade lymphomas High-grade lymphomas

Composed of big, ugly, aggressive cells.

• Follicular lymphoma• MALT lymphoma• Mycosis fungoides

• Large-cell lymphoma• Burkitt lymphoma

• Follicular pattern • “Butt” cells in blood• Grading is important for prognosis!• t(14;18)

Follicular Lymphoma

Things you must know

Follicular lymphoma: back to back follicles

Follicular lymphoma: three grades

Grade I Grade II Grade III

Mostly small cells

Relatively good prognosis

Small and large cells Mostly large cells

Relatively poor prognosis

Follicular lymphoma: “butt” cells in blood

Stage I

Stage II

Stage III

Stage IV

Single node

Two or more nodes onsame side of diaphragm

Lymph nodes on both sidesof the diaphragm

Diffuse extranodalinvolvement

90% 5ys

A = no additional symptomsB = weight loss, night sweats, fever

40% 5ys

Staging and Prognosis of Follicular Lymphoma

• Occurs in mucosa-associated lymphoid tissue• Associated with Helicobacter pylori• Early on, can be cured with antibiotics

Things you must know

MALT Lymphoma

• Skin lesions• Blood involvement• Cerebriform lymphocytes• T-cell immunophenotype

Things you must know

Mycosis Fungoides/Sézary Syndrome

Raised, nodular skin lesions

Pautrier microabscesses

Cerebriform lymphocytes

• Most common type of NHL• Large B cells• Extranodal involvement• Bad prognosis

Things you must know

Diffuse Large-Cell Lymphoma

“Diffuse” pattern = just sheets of cells, no follicles

Large lymphoma cells

• Children, young adults• Often presents with extranodal mass• Fast-growing and aggressive• Starry-sky pattern

Things you must know

Burkitt Lymphoma

Burkitt lymphoma

Starry-sky pattern

Burkitt lymphoma

Stars = tingible body macrophages (bystanders! not malignant!)

Sky = lymphoma cells

• Younger patients, good prognosis• Contiguous, predictable spread• Reed-Sternberg cell• Prognosis depends on stage

Things you must know

Hodgkin Lymphoma

Reed-Sternberg cell

Hodgkin lymphoma

• Malignant proliferation of plasma cells• Monoclonal gammopathy• Decreased normal immunoglobulins• Osteolytic lesions

Multiple Myeloma

Things you must know

• Weakness• Infections• Renal failure• Bone pain• Hypercalcemia

Clinical Features of Multiple Myeloma

Bone marrow: tons of plasma cells

Blood: rouleaux

Osteolytic lesions

Normal serum protein electrophoresis

Serum protein electrophoresis in myeloma

• Chemo and radiation• Bone marrow transplant• 5 year survival with chemo only: 20%

Treatment of Multiple Myeloma